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Martha Crowninshield brokered high-stakes business deals all the time as a venture capitalist.

But never before had she been involved in a deal with a payoff that could help millions of people worldwide. Crowninshield is a major player in a landmark effort to search the human genome for genes that put people at risk for multiple sclerosis.

There's no cure for MS today, and even with the best minds at Harvard, Cambridge University and elsewhere searching the genome, there might not be a cure tomorrow or even a decade from now.

Still, Crowninshield, a former partner at the investment firm Boston Ventures, is banking on the project. She, like an estimated 2.5 million people worldwide, has MS, an incurable disease of the central nervous system. She believes the team effort, which involves scientists from all over the world, eventually will lead to improved treatments and maybe something better.

"What we're looking for here is not a Nobel Prize but for a cure for this illness — this insidious illness," she says.

In 2002, Crowninshield learned about the International Multiple Sclerosis Genetics Consortium. After researching the project, she put $1 million of her own money into the project. "I wanted to be able to say I believe in this," she says. She also helped the scientists involved put together a business plan, which was crucial in selling the project to private investors as well as the National Institutes of Health and the National Multiple Sclerosis Society.

So far, the team has raised $15 million — just $5 million short of the money required for a massive five-year gene hunt for MS, says Adrian Ivinson, director of the Harvard Center for Neurodegeneration and Repair, the center that's managing the project and leading the consortium's fundraising.

Project scientists plan to collect blood from 1,000 people with MS and 2,000 healthy controls. Using a recently developed genetic roadmap, the team will look for "misspellings" in the DNA that put people at risk of developing the disease. Ultimately the team hopes to find the many genes thought to play a role in MS. If successful, the research could lead to drugs that could stop or even prevent MS.

"This will be the most powerful genetic study that has ever been undertaken for MS or for any other disease," says Harvard Medical School's Mark Daly. He's one of the scientists who produced a genetic road map that the group is using to hunt for MS genes.

A genetic spell-checker?

Daly and his colleagues found that human DNA is almost identical from person to person except for chunks of variations in the coding known as haplotypes. They produced the so-called HapMap that charts the location of the most common haplotypes, many of which are thought to involve misspellings which might lead to diseases such as MS.

Other scientists are now using the HapMap to search for the genetic basis of other killer diseases such as cancer and heart disease.

MS is thought to be an autoimmune disease in which the body's own immune cells attack the thick sheath, or myelin, that insulates the long fibers of nerve cells, says David Hafler, an immunologist and MS expert at the Harvard Medical School. That attack causes the symptoms of the disease, such as numbness, difficulty walking and loss of vision, he says.

Some diseases, like cystic fibrosis, are caused by an error or mutation in a single gene. MS, in contrast, is probably caused partly by variations in the DNA that make up the coding of not just one, but many genes, says John Richert, vice president for research at the National Multiple Sclerosis Society in New York.

The current thinking is that genes alone don't cause MS but simply make a person vulnerable to the disease, he says. People who inherit these genes probably are at risk but need another factor — perhaps exposure to a virus — to develop the disease, he adds.

Resources mobilized

Technicians at Harvard and MIT's Broad Institute are extracting the DNA from blood samples collected from the people in the study and are running the purified DNA through computers. They're using newly developed DNA chips that read the genetic code to search for misspellings that might be associated with MS.

"The data's looking beautiful," Hafler says. "I hope by the end of the year to have an answer."

Five drugs are available today to treat MS. But those therapies can't stop the disease from the get-go, a goal that Hafler would like to reach. He says that once the disease gets started, it's hard to repair the damage.

Looking toward the future

But the gene hunt might not pan out. The method the scientists are using might not be powerful enough to spot the genes involved in this complex disease, Richert says. That's a gamble that Crowninshield's willing to take.

Meanwhile Crowninshield must cope with flare-ups in her disease, flare-ups that cause temporary vision loss and difficulty walking. So she does all that she can do to reduce the risk of having an MS attack.

That's why in 2000 she gave up her job as a venture capitalist: She was afraid the stress of working round the clock would trigger attacks and possibly speed the progress of her illness.

She also believes that her fundraising and business advice for the MS project will make a difference, at least in the future.

"I don't expect anything to come of this to help me," she says. "But I do want to help the next generation."

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